Pharmacokinetic behaviour of R-(+)- and S-(-)-amlodipine after single enantiomer administration
Pharmacokinetic behaviour of R-(+)- and S-(-)-amlodipine after single enantiomer administration
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DOI：
10.1016/s0378-4347(97)00394-0
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发表时间：
1997-12-05
影响因子：
3
通讯作者：
Milutinovic, S
中科院分区：
文献类型：
--
作者：
Luksa, J;Josic, D;Milutinovic, S
安替洛尔，5-甲基-2-[（2-氨基乙氧基甲基）-4-（2-氯苯基）-1，4-二氢-6-甲基-3，5-吡啶二羧酸3-乙酯，是一种手性钙拮抗剂，目前已上市，作为外消旋体用于治疗。研究了健康男性志愿者单对映体给药后R-（+）-和S-（-）-β-内酰胺的药代动力学行为，以及两种对映体的外消旋混合物的比较给药。研究了血浆水平随时间的变化，并采用对映选择性色谱法（手性和非手性HPLC联用）结合在线固相萃取和UV吸光度检测进行测定。分别对R-（+）-和S-（-）-对映异构体的方法进行了验证。研究结果表明，单对映体给药后R-（+）-和S-（-）-噻托溴铵的药代动力学行为与外消旋体给药后各对映体的药代动力学行为相当。单一对映体给药后，人血浆中未发生体内外消旋。(C)1997年Elsevier Science B.V.
Amlodipine, 3-ethyl 5-methyl-2-[(2-aminoethoxymethyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate, is a chiral calcium antagonist, currently on the market and in therapeutic use as a racemate. The pharmacokinetic behaviour of R-(+)- and S-(-)-amlodipine after single enantiomer administration to healthy male human volunteers together with comparative administration of the racemic mixture of both enantiomers were studied. Plasma levels were studied as a function of time and assayed using an enantioselective chromatographic method (coupled chiral and achiral HPLC) with on-line solid-phase extraction and UV absorbance detection. The method was validated separately for the R-(+)- and S-(-)-enantiomer, respectively. Results of the study indicate that the pharmacokinetic behaviour of R-(+)- and S-(-)-amlodipine after single enantiomer administration is comparable to that of each enantiomer after administration of the racemate. No racemization occurs in vivo in human plasma after single enantiomer administration. (C) 1997 Elsevier Science B.V.